Quest Issue 2, Summer 2019

MDA.ORG/QUEST ISSUE 2 • 2019

EMPOWERING FAMILIES WITH INFORMATION AND INSPIRATION targeting

Researchers FLIP OVER TO READ SPECIAL look to treat EDITION: genetic 2019 MDA disease at CLINICAL & genes SCIENTIFIC its source CONFERENCE

ACCESSIBLE AIR TRAVEL How to get your travel plans off the ground 2019_Sarepta_corporate_FullPgAd_Quest_v4.indd 1 4/23/2019 12:52:48 PM A WORD FROM MDA FORWARD

MDA is committed to transforming Progress in Motion the lives of people affected by muscular dystrophy, ALS and from related neuromuscular diseases e are pleased to share content through innovations in science our 2019 Clinical & Scientific Conference, and innovations in care. Since our Wthemed “Progress in Motion,” in this special inception, MDA has committed issue of Quest. The conference, which was our largest more than $1 billion to accelerate ever, was held April 14–17 in Orlando, Fla. More than the discovery of therapies and 1,200 people attended, including academic scientists, cures. MDA supports the largest clinical researchers, clinical practitioners, industry network of multidisciplinary clinics scientists, regulatory scientists and leaders from other providing best-in-class care at funding organizations, such as patient advocacy groups more than 150 of the nation’s top and government institutions. medical institutions and serves the This was the first time MDA has convened both our community through MDA Summer scientific and clinical communities for one large event. Camp, the Resource Center and We merged these previously separated meetings because educational conferences, events Lianna Orlando, Ph.D. and materials for families and both fields have matured, and our community of experts healthcare providers. is increasingly meeting in the center on therapy development. MDA’s conference serves as a call to action for For advertising opportunities: all stakeholders and an opportunity to facilitate collabo- Patty MacEwan ration across disciplines. TURN ME National Director of Corporate AROUND! The major themes highlighted Partnerships Flip over this edition [email protected] at this year’s conference included genetic medicine, clinical trials, of Quest for a special For editorial queries: emerging use of technology and section about MDA’s [email protected] newborn screening. Each of the 2019 Clinical & Scientific To update personal information and your conference sessions was designed to Conference. You’ll Quest subscription status, contact the illustrate common lessons that cut find highlights and key MDA Resource Center at 833-ASK-MDA1 . across the different disease states takeaways from in-depth Quest Volume 26, Issue 2 and fields that we serve. Presenters sessions exploring the Published quarterly by traded learnings across diseases on latest in neuromuscular Muscular Dystrophy Association disease research and 161 N. Clark St., Suite 3550 common features of biology, approaches to drug devel- Chicago, IL 60601 | (800) 572-1717 opment, laboratory and clinical techniques, and other care. For more confer- email: [email protected] Available on the internet at mda.org/quest rapidly evolving topics. ence coverage, visit ISSN 1087-1578 Postage paid at Bolingbrook, IL Other conference highlights included a keynote mda.org/quest. Nonprofit postal permit number 1446. speech by Janet Woodcock, M.D., director of the Center

Postmaster: Treat as Standard A Mail Only for Drug Evaluation and Research at the U.S. Food and © 2019, Muscular Dystrophy Association. All rights Drug Administration (FDA); a panel discussion by additional FDA experts; an introduc- reserved. MDA and QUEST are registered trademarks of the Muscular Dystrophy Association. tion to MDA’s 2019 National Ambassadors; and an exhibit hall featuring a Technology The acceptance of advertising in this magazine does not constitute or imply endorsement by MDA of any Row and a Patient Advocacy Pavilion. product or service. MDA accepts no responsibility for any claims made in any advertisement. Quest reserves This year’s conference was the largest and most comprehensive of its kind in MDA’s the right to refuse to accept any advertisement. For advertising information, call (703) 582-8476. history. And for 2020, we’re aiming even higher. Information contained in Quest may not be reproduced, published, transmitted or distributed in whole or in part without prior written consent of MDA. Always consult your professional advisers as to how medical, legal or financial information in Quest pertains to you. MDA assumes no liability for any information Sincerely, in Quest.

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PUBLICATION MANAGEMENT Lianna Orlando, Ph.D. Interim Head of Research Muscular Dystrophy Association GLCDELIVERS.COM Quest MDA.ORG/QUEST 1 32

issue 2 • 2019 CONTENTS

DEPARTMENTS FEATURES 04 16 pg 30 CONNECT & LEARN TARGETING GENES Join an upcoming MDA Researchers look to treat genetic disease at its source. Engage educational event.

06 MORE ONLINE PROGRESS NOW Read the latest news on BREAKING NEWS medical research, scientific On May 24, the advances and clinical trials. U.S. Food and Drug Administration (FDA) approved Zolgensma 14 (onasemnogene THRIVE 365 DEPARTMENTS abeparvovac-xioi), Navigate the ups and downs a one-time gene- of accessible air travel. 26 32 replacement therapy SPOTLIGHT FROM WHERE I SIT for the treatment of Neurologist Tetsuo A hiker takes on children younger than Ashizawa, M.D., answers Mount Kilimanjaro and 2 with spinal muscular questions about myotonic proves she is stronger atrophy (SMA). This dystrophy (DM). than FSHD. approval marks another historic achievement for 30 34 the SMA community. ACCESS MDA LASTING Read more about it on A doctor goes above and IMPRESSION MDA’s Strongly blog. beyond at MDA Summer Brotherly love fuels Go to strongly.mda. Camp, a Florida mom is a fire fighter’s org and search for running strong with Team dedication to “Zolgensma.” Momentum and more. Fill the Boot. MDA-028

2 Quest ISSUE 2 • 2019 COOLCORE® NOW COMES STANDARD ON ALL ADI BACK CUSHIONS The patented, award-winning CoolCore® fabric wicks moisture away from your body, helping keep you dry and comfortable. The chemical-free fabric allows cushions to cool better and last longer—a perfect combination for your busy life. Stay chill with CoolCore and ADI.

Learn more at StealthProducts.com CONNECT & LEARN MDA ENGAGE EVENTS ACROSS THE COUNTRY

A Day to Learn Together

We believe in the power of community and the importance of building relationships with others going through similar experiences. If you are living with a neuromuscular disease, we invite you and your loved ones to attend our MDA Engage education events taking place across the country. MDA Engage Community Education wSeminars and Disease Specific Sym- posia are one-day events empowering individuals and families with knowledge and resources. Information is shared by experts in the field and individuals living with neuromuscular disease.

EVENT SPOTLIGHT On April 12, the spinal muscular atrophy (SMA) community came together for the MDA Engage SMA Symposium in Orlando, Fla. Event Chair Richard S. Finkel, M.D., the chief of Neurology at Nemours Children’s Hospital, shared updates on research Above: participants at an MDA Engage SMA Symposium in Orlando, Fla. Bottom right: a panel on SMA. within SMA. Participants also heard about managing scoliosis and contractures and the importance of multidisciplinary care within MDA Care UPCOMING MDA ENGAGE EVENTS Centers. A family panel discussed care and social needs while living with SMA. Representatives from Biogen, Genentech and • Aug. 3, 2019 MDA Engage Community Education AveXis joined a panel with physicians to discuss developing Seminar, Dallas, TX drugs for SMA. • Sept. 7, 2019 MDA Engage Community Education Seminar, Oklahoma City, OK • Sept. 14, 2019 MDA Engage Community Education Seminar, San Diego, CA • Oct. 5, 2019 MDA Engage Community Education Seminar, Nashville, TN • Nov. 2, 2019 MDA Engage MG Symposium, Durham, NC • Nov. 9, 2019 MDA Engage DMD Symposium, Sacramento, CA • Nov. 9, 2019 MDA Engage CMT Symposium, Philadelphia, PA • Nov. 9, 2019 MDA Engage Myotonic Symposium, Rochester, NY

Find an Event For a complete list of MDA Engage events and to register, visit mda.org/care/mda-engage.

Quest 4 ISSUE 2 • 2019 ADVERTISEMENT

IMAGI NE IF GENE REPLACEMENT THERAPY COULD HELP CHANGE LIVES.

GENE REPLACEMENT THERAPY is changing the way we see genetic diseases. By targeting faulty or missing genes, this innovation is creating a new world of opportunities and potentially helping people living with genetic diseases.

Discover more about this scientific advancement at ExploreGeneTherapy.com

Amyotrophic lateral sclerosis (ALS)

Stem Cell Study Participants Needed Researchers will evaluate effects of patient’s own modified stem cells on disease progression

Researchers at Brainstorm Cell outpatient procedure. The cells see their regular doctor for Therapeutics are looking for are cultured to secrete higher Human routine care. individuals with ALS to par- levels of chemicals that protect Bone In order to be eligible to participate in a phase 3 study to neurons, or neurotropic factors. Hematopoietic ticipate, adults 18-60 years old help researchers evaluate the The cells are transplanted back stem cells with ALS must have a disease into the patient, where they can effects of mesenchymal stromal Mesenchymal duration from symptom onset stem cells secreting neuro- potentially benefit the health stem cells of 24 months or fewer; if taking (bone marrow) trophic factors (MSC-NTF and survival of neurons, slowing riluzole, have a stable dose or cells) on disease progression. the progression of the disease. not have taken the drug for 30 In ALS, motor neurons degen- Trial participants will be MSC-NTF cells are harvested from the days prior to first study visit; erate or die and stop sending randomly assigned to groups bone marrow in an outpatient procedure. and meet additional criteria. messages to muscles, which grad- receiving either MSC-NTF cells ually weaken and waste away. or placebo. Researchers will associated with slowing the To learn more about this MSC-NTF cells are the patient’s use the ALS Functional Rating rate of the disease. study, visit ClinicalTrials. own (autologous) cells harvested Scale-Revised to determine Throughout the study, gov and enter NCT03280056 in from the bone marrow in an whether the treatment is participants will continue to the “Other Terms” search box.

Quest 6 ISSUE 2 • 2019 MDA MVP Grant Supports AcuraStem ALS Drug AS2015 may help prevent motor neuron death

MDA awarded an MDA Venture make drug development easier The investigational treat- Philanthropy (MVP) grant totaling and less risky. ment has the potential to be $300,000 over two years to The grant will allow transformative for a broad range California-based biotechnology AcuraStem to undertake proof- of ALS patients. AcuraStem company AcuraStem to support of-concept studies in mouse aims to begin clinical trials in preclinical development of a new models of ALS, as well ALS patients by 2020.

“ With this funding, we’ll continue to small molecule therapeutic for as develop biomarkers for its move forward our novel approach ALS. MVP grants are awarded to orally delivered, blood-brain- Learn more about MDA’s aimed at transforming outcomes for researchers developing therapeu- penetrating, preclinical develop- ALS.” —AcuraStem Co-Founder and ALS research efforts at Board Chairman Paul August, Ph.D. tics for neuromuscular diseases to ment candidate, AS2015. mda.org/science.

ORARIALS-01 Biogen to License and Now Enrolling Phase 3 clinical trial will assess effects of Develop BIIB067 arimoclomol on ALS disease progression Antisense drug may block production of flawed SOD1 protein Researchers at Orphazyme are looking for participants with ALS for the ORARIALS-01 phase 3 Following its announcement of positive phase 1 clinical trial study to evaluate the effects of arimoclomol on results, Biogen Inc. will license and develop partner Ionis disease progression. Pharmaceuticals’ BIIB067 (IONIS-SOD1RX). BIIB067 is an Arimoclomol is designed to work by helping the investigational therapy for ALS caused by superoxide dis- body clear abnormally aggregated proteins from cells. mutase 1 (SOD1) mutations, a subtype of familial ALS. The trial aims to determine whether treatment with arimo- BIIB067 is an antisense oligonucleotide (ASO), a molecule clomol is associated with slowing the rate of functional and that is composed of short segments of synthetic genetic mate- respiratory decline and extending survival as measured by rial (nucleic acid) that bind to RNA, the chemical step between Combined Assessment of Function and Survival (CAFS). DNA and the protein that it manufactures. When an antisense Trial participants will randomly be assigned to groups that molecule like BIIB067 binds to RNA, it prevents or decreases will receive either arimoclomol or placebo. Total study duration protein production. for each participant will be up to 82 weeks, with a clinic visit The study was designed to evaluate the safety and tolerabil- approximately every two months to assess patient function using ity of BIIB067, as well as how the drug is absorbed, distributed ALS-specific assessment scales. Throughout the study, partici- and metabolized in the body. Participants who received the pants will continue to see their regular doctor for routine care. highest dose over three months showed significantly lower To participate, adults ages 18 and older must have an ALS levels of SOD1 protein in the cerebrospinal fluid and reduced diagnosis, with disease duration from symptom onset of 18 months clinical decline, as measured by the ALS Functional Rating or fewer, and meet additional study criteria. Scale-Revised, when compared to the placebo group.

For more information on this study, go to ClinicalTrials.gov To learn more about this trial, visit ClinicalTrials.gov and and enter NCT03491462 in the “Other Terms” search box. enter NCT02623699 in the “Other Terms” search box. Visit orphazyme.com/about-arimoclomol to learn more about arimoclomol.

Quest MDA.ORG/QUEST 7 PROGRESS NOW RESEARCH AND CLINICAL TRIAL UPDATES

Charcot-Marie-Tooth disease (CMT) MDA and CMTA Co-Fund Research Studies will assess gene delivery paradigms in CMT1X

The Charcot-Marie-Tooth Association (CMTA) and of CMT (CMT1X), which affects approximately 1 in 25,000 people. MDA have jointly awarded a research grant totaling Using this grant funding, Dr. Kleopa will perform critical proof- $276,430 over three years to Kleopas Kleopa, M.D., of-concept studies to test whether delivery of the Cx32 gene using professor and senior consulting neurologist at the an adeno-associated virus (AAV) vector (delivery vehicle) can Cyprus Institute of Neurology and Genetics, Cyprus improve symptoms in a mouse model of CMT1X as well as deter- School of Molecular Medicine, in Nicosia, Cyprus. mine the optimal route for delivery of the therapy. Mutations in the gene coding for the gap junc- tion beta-1 protein (GJB1), also known as connexin Learn more about MDA-supported CMT 32 (Cx32), are associated with the X-linked form research at mda.org/science.

Duchenne muscular dystrophy (DMD) Vamorolone Study Encouraging Preliminary Seeks Participants Results for IGNITE DMD Researchers will assess drug safety and efficacy Gene therapy trial tests dosages of SGT-001

Researchers at ReveraGen 16 clinic visits. Throughout the Solid Biosciences BioPharma are looking for study, participants will continue has announced pre- ambulatory boys with DMD to see their regular doctor for liminary results from to participate in a phase 2b routine care. its phase 1/2 clinical study to evaluate the safety To be eligible to partici- trial, called IGNITE and efficacy of vamorolone. pate, candidates must have a DMD, which is Researchers hope this therapy confirmed diagnosis of DMD, designed to assess will improve muscle strength be between the ages of 4 the safety and efficacy of its lead drug candidate, SGT-001, in and endurance with a more and 7, and meet additional children and adolescents with DMD. favorable safety profile com- study criteria. DMD is caused by a mutation in the dystrophin gene on the pared to the current standard Travel support for the X chromosome that results in little or no production of dystro- of care. participant and one travel com- phin, a protein that is essential for keeping muscle cells intact. Participants will randomly panion for each visit is available. SGT-001 is a type of gene therapy that delivers an engineered be assigned to groups that Contact Suzanne Gaglianone replacement gene called “microdystrophin” via intravenous (IV) will receive either vamorolone at suzanne.gaglianone@ infusion, which enables production of a functional protein to or placebo during treatment reveragen.com for more infor- substitute for the missing dystrophin. period No. 1 (lasting 24 weeks); mation about travel support. Learn about the study design and encouraging results all participants will receive reported at the MDA Clinical & Scientific Conference. Flip this issue vamorolone in treatment To learn more or and turn to page 5. period No. 2. to inquire about The total study duration participation, contact For more information on IGNITE DMD, go to ClinicalTrials. for each patient will be about Andrea D’Alessandro at gov and enter NCT03368742 in the “Other Terms” one year, with approximately [email protected]. search box.

Quest 8 ISSUE 2 • 2019 Innovative Exon Limb-girdle muscular dystrophy (LGMD) Skipping Trial WVE-210201 moves to phase 2/3 trial Positive Results for

Wave Life Sciences’ phase 2/3 clinical trial of suvodirsen MYO-101 Gene Therapy (WVE-210201), an investigational therapy for boys with DMD who Trial aims to enroll more symptomatic are amenable to exon 51 skipping, has been selected by the U.S. individuals between ages 4 and 15 Food and Drug Administration (FDA) for its complex innovative trial designs (CID) pilot program. Sarepta Therapeutics has announced For more The FDA’s CID pilot program aims to improve clinical trial positive interim results of a phase 1/2a information design and help streamline and advance drug development and clinical trial for MYO-101, a gene ther- about the trial, regulatory approval. Wave’s application included a plan to leverage apy candidate developed by Myonexus visit ClinicalTrials. DMD historical control data to effectively reduce the number of Therapeutics for people living with gov and enter patients needed in the placebo group, potentially accelerating the LGMD type 2E (LGMD2E). Also known NCT03652259 in completion of the study. as beta-sarcoglycanopathy, LGMD2E is the “Other Terms” Learn about the promising results of Wave’s phase 1 study characterized by insufficient levels of search box. reported at the MDA Clinical & Scientific Conference. Flip this beta-sarcoglycan protein. issue and turn to page 8. The first three trial participants dosed demonstrated significant increased production of For more information on WVE-210201, visit beta-sarcoglycan protein in the muscle fiber. Individuals also wavelifesciences.com. demonstrated a marked reduction in an enzyme (creatine > PROGRESS NOW RESEARCH AND CLINICAL TRIAL UPDATES

kinase, or CK) that muscles release in response to damage. moving ahead with cohort 2, which will include three individuals This trial was the first LGMD gene therapy trial to use a single, treated with a higher dose and three placebo subjects. Placebo intravenous infusion to restore expression and functionality of subjects will have the option to be treated with the experimental beta-sarcoglycan in skeletal and cardiac muscle. Based on data therapy once biopsy results have been taken after one year reported from the first, low-dose cohort, Sarepta indicated it is of participation. Mitochondrial myopathy (MM) Myasthenia gravis (MG) Firdapse Trial Drug was shown to be safe and Elamipretide is administered by subcutaneous injection. effective in phase 2 trial Results from a phase 2b clinical trial to evaluate Firdapse (amifampridine phosphate) for the treatment of muscle- specific kinase antibody positive myasthenia gravis (MuSK-MG) showed the drug to be safe and effective in MMPOWER-3 treating people with this rare disease. MuSK is a protein that plays an important role in the for- Recruiting mation and maintenance of the connection between nerve and muscle. Patients with MuSK-MG produce antibodies Participants that attack this protein, resulting in a reduced ability of nerves to communicate with muscles. Phase 3 trial will assess effects of elamipretide In the range of a 30 to 60 mg daily dose, Firdapse was found to be safe and effective for treating patients with Stealth BioTherapeutics is looking for participants with pri- MuSK-MG. All 10 enrolled participants showed statistically mary mitochondrial myopathy (PMM) to participate in the significant changes in both Quantitative Myasthenia Gravis MMPOWER-3 phase 3 trial. This trial is designed to evaluate (QMG) and Myasthenia Gravis-Activities of Daily Living the efficacy and safety of daily subcutaneous (under-the-skin) (MG-ADL) scores, as well as improved assessments of qual- injections of elamipretide, an investigational drug that has been ity of life (using the Myasthenia Gravis Quality of Life scale) shown to improve mitochondrial function in preclinical and early and fatigue (using the Fatigue Severity scale). The only clinical studies. adverse event was a burning or prickling sensation (pares- Participants will randomly be assigned to groups that will thesia) in 60 percent of patients. receive treatment with either elamipretide or placebo for six Recruitment is ongoing for a phase 3 clinical trial (identi- months. Researchers will assess whether treatment with elami- fier NCT03579966) testing Firdapse in MuSK-MG patients. pretide is associated with increased distance in the six-minute walk test and decreased patient-reported fatigue. Firdapse is an Participants who complete the six-month study may elect oral potassium channel inhibitor to extend their treatment and receive elamipretide for the designed to remaining duration of the trial. prolong signals released from To participate in MMPOWER-3, individuals must: nerves and allow >> Have previous genetic testing results available greater stimula- tion of muscles. >> Be able to walk >> Be between ages 16 and 80 >> Be diagnosed with PMM in the opinion of the investigator >> Be able to meet additional study criteria

Learn more about the study at stealthbt.com. For questions, or to inquire about participation, contact Cristy Balcells R.N., Read more about Firdapse at M.S.N., at [email protected] or 423-914-8322. catalystpharma.com.

Quest 10 ISSUE 2 • 2019 Positive Results Pompe disease Rozanolixizumab associated with (acid maltase deficiency, AMD) improvement in health and quality of life Pharmaceutical company UCB has Study for Adults with announced positive results in its phase 2 trial of rozanolixizumab (also known as UCB7665), a potential treatment for MG. Pompe Disease Investigators found that rozanolixizumab, Combination therapy targets late-onset a neonatal Fc receptor monoclonal antibody, Pompe disease performed well in the study, achieving improvement in multiple disease-related endpoints and a satisfactory safety profile. Researchers at Amicus Therapeutics are looking for adults The randomized study enrolled 43 participants living with with late-onset Pompe disease (LOPD) to participate in a MG and evaluated patients who received the drug vs. placebo phase 3 study called PROPEL. The study aims to evaluate based on the following pre-specified disease-related endpoints: the safety and efficacy of ATB200/AT2221, which researchers Quantitative Myasthenia Gravis (QMG) score, Myasthenia hope may improve muscle function and respiratory function Gravis Composite (MGC) responder rate and Myasthenia compared to the current standard of care. Gravis-Activities of Daily Living (MG-ADL) score. Learn about interim trial results reported at the MDA Clinical Recipients of rozanolixizumab saw improvements in both & Scientific Conference. Flip this issue and turn to page 9. qualitative outcomes and biomarkers. To learn more, visit pompestudy.com. To inquire about To learn more about the phase 2 trial of participation, contact [email protected]. rozanolixizumab, visit ucb.com.

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Monitor The information presented is not comprehensive. Talk Visit www.PTCCares.com blood glucose at regular intervals. For patients with to your healthcare provider for more information or hyperglycemia, anti-diabetic treatment should be see www.EMFLAZA.com for the full FDA-approved for more information. initiated or adjusted accordingly. product information. Increased Risk of Infection: Medical advice should be For medical information, product complaints, or to sought immediately if you develop a fever or other report an adverse event, please call 1-866-562-4620 or signs of infection as some infections can potentially email at [email protected]. be severe and fatal. Avoid exposure to chickenpox or EMFLAZA is indicated for the treatment of Duchenne measles, but if you are exposed, medical advice should You may also report adverse events directly to FDA at muscular dystrophy in patients 5 years of age and older. be sought without delay. 1-800-FDA-1088 or www.fda.gov/medwatch.

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EMF000260_QUEST PTC CARES_PF2.indd All Pages 3/21/19 2:29 PM ADVERTISEMENT ADVERTISEMENT SELECTED IMPORTANT SAFETY EMFLAZA and you should seek medical attention if INFORMATION psychiatric symptoms develop. Effects on Bones: There is a risk of osteoporosis or What is EMFLAZA? decrease in bone mineral density with prolonged use of EMFLAZA® is a corticosteroid indicated for the EMFLAZA, which can potentially lead to vertebral and treatment of Duchenne muscular dystrophy (DMD) in long bone fractures. patients 5 years of age and older. Effects on Growth and Development: Long-term use of corticosteroids, including EMFLAZA may slow growth When should I not use EMFLAZA? and development in children. • Do not use if you are allergic to deflazacort or any of Ophthalmic Effects: EMFLAZA may cause cataracts the inactive ingredients in EMFLAZA or glaucoma and you should be monitored if What should I tell my healthcare provider before corticosteroid therapy is continued for more than YOUR TREATMENT NEEDS taking EMFLAZA? 6 weeks. It is important to tell your healthcare provider if you Vaccination: The administration of live or live ARE OUR PRIORITY have had recent or ongoing infections, develop a fever, attenuated vaccines is not recommended. Killed or have recently received a vaccine or are scheduled for a inactivated vaccines may be administered, but the PTC Cares™ is a patient support program vaccination, or experience any other side effects. responses cannot be predicted. that provides personalized case management Serious Skin Rashes: Seek medical attention at the first support before your first prescription and What warnings should I know about EMFLAZA? sign of a rash. throughout treatment. Do not stop taking EMFLAZA, or change the amount you are taking, without first checking with What are the side effects that could occur with your healthcare provider, as there may be a need for EMFLAZA? gradual dose reduction to decrease the risk of adrenal • facial puffiness or Cushingoid appearance insufficiency and steroid “withdrawal syndrome”. • weight increased Acute adrenal insufficiency can occur if corticosteroids • increased appetite are withdrawn abruptly, and can be fatal. A steroid • upper respiratory tract infection “withdrawal syndrome”, seemingly unrelated to • cough adrenocortical insufficiency, may also occur following • frequent daytime urination PTC Cares is abrupt discontinuance of corticosteroids. • unwanted hair growth For patients already taking corticosteroids during times • central obesity here to help with: of medical stress, the dosage may need to be increased. • colds • Benefits investigation support Cushing’s Syndrome: Cushing’s syndrome occurs with What other medications might interact with prolonged exposure to exogenous corticosteroids, EMFLAZA? including EMFLAZA. Symptoms include high blood Certain medications can cause an interaction with • Information about pressure, truncal obesity and thinning of the limbs, EMFLAZA. Tell your healthcare provider of all the EMFLAZA® (deflazacort) purple striae, facial rounding, facial plethora, muscle medication you are taking, including over-the-counter weakness, easy and frequent bruising with thin fragile and PTC Cares services Call 1-844-4PTCCARES medicines (such as insulin, aspirin, or other NSAIDS), skin, posterior neck fat deposition, osteopenia, acne, dietary supplements, and herbal products. Alternate (1-844-478-2227) amenorrhea, hirsutism, and psychiatric abnormalities. • Securing access to EMFLAZA treatment, dosage adjustment, and/or special test(s) 8 am - 8 pm ET Monday - Friday Hyperglycemia: Corticosteroids can increase blood may be needed during treatment. Do not take to speak with a glucose, worsen pre-existing diabetes, predispose EMFLAZA suspension with grapefruit juice. PTC Cares case manager. those on long-term treatment to diabetes mellitus, and may reduce the effect of anti-diabetic drugs. Monitor The information presented is not comprehensive. Talk Visit www.PTCCares.com blood glucose at regular intervals. For patients with to your healthcare provider for more information or hyperglycemia, anti-diabetic treatment should be see www.EMFLAZA.com for the full FDA-approved for more information. initiated or adjusted accordingly. product information. Increased Risk of Infection: Medical advice should be For medical information, product complaints, or to sought immediately if you develop a fever or other report an adverse event, please call 1-866-562-4620 or signs of infection as some infections can potentially email at [email protected]. be severe and fatal. Avoid exposure to chickenpox or EMFLAZA is indicated for the treatment of Duchenne measles, but if you are exposed, medical advice should You may also report adverse events directly to FDA at muscular dystrophy in patients 5 years of age and older. be sought without delay. 1-800-FDA-1088 or www.fda.gov/medwatch.

EMF000260_QUEST PTC CARES_PF2.indd All Pages 3/21/19 2:29 PM THRIVE 365 HEALTH, WELLNESS AND INDEPENDENT LIVING The Ups and Downs of Accessible Air Travel A little knowledge and preparation can get your travel plans off the ground

BY BARBARA AND JIM TWARDOWSKI

policies is also vital for a smooth flight.

TRAVELING WITH EQUIPMENT The ACAA requires newer airplanes to have space in the cabin to store a folded wheelchair or other compact mobility equipment. A power wheelchair or other bulky equipment will fly in the baggage compartment. Lee removes the headrest and seat cushion from his power wheelchair and carries them onto the plane for safekeeping. “Know the dimensions of the plane’s cargo hold in advance,” advises John Morris, Cory Lee believes the rewards of travel ory Lee, who lives Travel for Wheelchair Users,” the founder of Wheelchair- outweigh the hassles. with spinal muscu- emphasizes that travelers Travel.org. This helps you Clar atrophy (SMA), with disabilities should be determine if your wheelchair has explored 32 countries familiar with the Air Carrier will have to be disassembled, in the past five years. While Access Act (ACAA). which the ACAA requires traversing the globe in his Passed in 1986, the ACAA airline staff to assist with at 300-pound power wheelchair, prohibits discrimination on the the airport. Morris, a triple Lee writes about accessible basis of disability and requires amputee who uses a power travel on his blog curbfree airlines to provide certain wheelchair, provides a list of withcorylee.com, which has accessible facilities and accom- airplanes and their cargo hold garnered thousands of follow- modations. The ACAA applies dimensions on his website. ers. The No. 1 topic people to all U.S. airlines and flights It’s a good idea to ask your Traveler Resource ask him about is air travel. on foreign carriers to or from wheelchair manufacturer how MDA’s Accessible Air Travel For passengers with the United States. to properly disassemble or Resource Center helps you neuromuscular diseases — “Knowing the rules and fold the seatback for storage find important information especially those who use regulations gave me more during flight. Attach written about airports, airlines and wheelchairs — air travel confidence about flying,” instructions to your chair your rights as a traveler. requires knowledge and Lee says. before you check it. “Other- Visit cqrcengage.com/mda/ preparation. Lee, who wrote Being familiar with air- wise, your chair will be loaded accessibleairtravel. a book on the subject, “Air port procedures and airline on its side, which is the No. 1

Quest 14 ISSUE 2 • 2019 the plane. The ACAA states that passengers INFORMED CONSUMERS with disabilities who need assistance or In December 2018, a new law, championed by MDA, went extra time to board into effect requiring airlines to report to the U.S. Department should go before all of Transportation (DOT) how many wheelchairs and motor- other passengers, but ized scooters they break, lose or damage each month. This Morris sees this reg- rule gives airline consumers more information to compare ulation violated often. airlines and make informed decisions about their equipment. Speak with a gate Find information about mishandled equipment, as well agent before boarding as flight delays and consumer complaints, in the DOT’s starts to make sure Air Travel Consumer Reports at transportation.gov/ you can pre-board. individuals/aviation-consumer-protection/ Airlines are required air-travel-consumer-reports. to provide assistance To learn more about consumer rights and how to file with boarding for a complaint, visit transportation.gov/airconsumer. those who need it. If Cory Lee gets assistance boarding a plane. you cannot walk to your seat, airline staff 30,000 feet. Only wide-body way it is broken and damaged,” will roll you to your seat in a aircraft (those with two aisles) Morris says. narrow, high-backed wheel- are required to have accessible Always carefully inspect chair and assist with a transfer. lavatories. However, the ACAA your equipment upon landing. Select a roomier bulkhead seat does require most flights to If it is damaged, immediately for easier transfers or confirm have a wheelchair on board to report it to the airline and the that your row has armrests help a passenger reach the lav- U.S. Department of Trans- that can be raised. atory if the passenger requests portation. (See “Informed it at least 48 hours in advance. Consumers.”) BATHROOM CONCERNS THE WORLD AWAITS GETTING ONBOARD Perhaps the biggest obstacle While long security lines and One of the most stressful to air travel is knowing what cramped airplane seats may be aspects of flying is boarding to do when nature calls at unavoidable, a little knowledge and advance planning can ensure that accessibility issues READY FOR TAKE-OFF don’t keep you grounded. “It’s too bad that people When planning your travel, follow these tips for a who are capable of traveling smooth flight: are staying home because >> Before you purchase a ticket, review the airline’s they are afraid of the expe- accessibility services and policies on its website. rience they might have with >> At least 48 hours before departing, call your airline’s air travel,” Morris says. “Air disability assistance phone line and request the travel is a barrier that can specific assistance you will need. be overcome. The world is >> Build extra time into your flight plan, especially if you waiting for you.” Q are catching a connecting flight, using large and busy airports, or traveling internationally. Remember, wheel- Barbara Twardowski lives chair users are the last passengers to exit the plane. with Charcot-Marie-Tooth >> Review the Transportation Security Administration disease (CMT) and uses a power (TSA) screening process at tsa.gov/travel/passenger- wheelchair. Jim, her husband, is support. For questions, call TSA (855-787-2227) at a registered nurse. The couple least 72 hours before flying. writes about accessible travel, health and lifestyle.

Quest MDA.ORG/QUEST 15 Researchers look to treat genetic disease at its source

BY AMY MADSEN

Quest 16 ISSUE 2 • 2019 TARGETING

Until the 1980s, little was known about the cause of any neuromuscular disease. In 1986, MDA-supported genesresearchers identified a single gene Uon the X chromosome that leads to Duchenne muscular dystrophy (DMD) when it is mutated (flawed). In 1987, the protein associated with that gene was identified and named dystrophin. Lack of the dystrophin protein in muscle cells causes them to be fragile and easily damaged.

Quest MDA.ORG/QUEST 17 Many more discoveries have been made since then, DELIVERING NEW GENES and scientists have identified Gene-replacement therapy follows these basic steps. thousands of genes that, when mutated, cause disease in humans. Identifying the 1 Scientists create a new, gene that causes a certain dis- working copy of a missing ease — and how the mutation or nonworking gene. leads to disease — gives hope for treatments and cures where none existed before. Without knowing the root cause of a disease, medical professionals 2 The new gene is inserted into a vector (often a can only treat the symptoms. harmless virus) that acts as the vehicle to carry But when the gene causing the the gene to its destination in the body. disease is identified and the mechanism behind the disease is understood, researchers have a potential target at which to aim treatments and cures. In recent years, drug developers have been able to pair the ever-expanding pool of gene identifications with advances in technologies for delivering gene-targeted therapies. These therapies 3 The vector is placed hold a great deal of promise in the body, where it for treating neuromuscular diseases, including many delivers its payload of the rare diseases under to the cellular control MDA’s umbrella. center — the nucleus. IT STARTS WITH GENES Genes are made up of DNA. 4 Inside the nucleus, the Some genes contain instructions for making proteins that new gene provides the body needs to function instructions for the properly. cell to make necessary Most neuromuscular protein. diseases are caused by genetic mutations. These mutations can result in the destruction, malfunction or absence of proteins needed for muscles to develop and function properly. Gene-targeted therapies seek to treat a genetic disease at its source. A therapy may do this by replacing a mutated gene with a working gene, repairing a flawed gene

Quest 18 ISSUE 2 • 2019 or altering how a gene body and treated in a lab. The Many scientists are work- is controlled. altered cells are then trans- ing with adeno-associated viral Words in blue are defined in “What “Gene therapy is an ferred back into the person. (AAV) vectors. These small Does That Mean?” opportunity to directly In vivo gene therapy involves viruses don’t cause diseases on page 20. impact patients with neuro- delivering genes directly into in people, but they can insert muscular disease,” says Barry a person’s body through an genetic material into cells. Byrne, M.D., Ph.D., director injection or intravenous (IV) AAVs are designed to allow of the Powell Gene Therapy tube inserted in a vein. a new gene to enter the cell Center at the University of nucleus and work on its own, Florida and a former MDA DELIVERING without integrating into the grantee. “Replacing the THE GOODS cell’s DNA, where it can trig- causative gene for a given An area of intense focus for ger unintended consequences, condition seems to have a researchers is the vector, such as other diseases. major effect where conven- which can determine whether The downside of not inte- tional therapies may not have a replacement gene integrates grating into the cell’s DNA an impact.” itself into the cell’s existing is that as cells divide, the DNA or remains separate transferred gene — and its GENE-REPLACEMENT inside the nucleus. effects — are gradually lost. THERAPY Currently, the most exciting area of gene-targeted therapy MDA’S GENE CATALYST is gene-replacement therapy, INITIATIVE DRIVES ADVANCES which aims to introduce a IN GENETIC MEDICINE working copy of a missing or defective gene into target cells. MDA recently launched our Gene Catalyst Initiative Zolgensma, a gene- (GCI), a multi-faceted effort to ensure that MDA replacement therapy for the families benefit from all the promise genetic medicine treatment of children younger has to offer. than 2 with spinal muscular atrophy (SMA), was recently The GCI comprises a number of initiatives: approved by the U.S. Food and >> Working to provide genetic diagnoses to individuals Drug Administration (FDA). with neuromuscular disease — the first step to making Zolgensma is the second-ever it possible for them to utilize genetic medicine approved gene-replacement >> Driving MDA Care Centers to become leading therapy for any disease and experts in genetic medicine the first for a neuromuscular >> Providing public education about genetic medicine disease. (To learn more about >> Continuing to fund cutting-edge research to advance studies of Zolgensma and how knowledge and develop safe and effective gene- the drug works, flip this issue targeted therapies and turn to page 7.) In gene-replacement “This important initiative builds upon MDA’s long therapy, scientists create the history of supporting research aimed at the develop- new gene in a laboratory and ment of genetic medicines, with an appreciation and then package it in a delivery understanding that the best way to move toward vehicle called a vector, which treatments and cures is to understand the root cause transports the gene into the of the disease and target that as closely as possible,” nucleus of targeted cells. The says Lianna Orlando, Ph.D., MDA’s interim head cells can “read” the code car- of research. ried within the new gene and Through the multi-pronged approaches embodied produce the needed protein. in the GCI, MDA will continue to work with its large There are two ways to community of partners — including families, donors, introduce the vector to cells. researchers and clinicians — to keep up the momentum In ex vivo gene therapy, cells and pave the way to more treatments and cures. are removed from a person’s

Quest MDA.ORG/QUEST 19 WHAT DOES THAT MEAN? Here is a guide to terms commonly used in discussing gene-targeted therapy. Antisense oligonucleotides: Small Genetic mutation: A flaw in a sections of DNA or RNA that can bind to sequence of DNA that alters specific molecules of RNA. This blocks the gene function. ability of the RNA to make a protein or work in other ways. Genome: The sum of all genes in the body. CRISPR-Cas9: A tool used to “edit” pieces of a cell’s DNA. Also called CRISPR, this Nonsense mutation: Also called a stop tool uses a specially designed RNA mole- mutation, this is a flaw in a sequence of cule to guide an enzyme called Cas9 to a DNA that causes cells to stop producing a specific sequence of DNA. Cas9 then cuts protein earlier than expected. This results in the strands of DNA and removes a small a shortened, usually nonfunctional protein. piece, causing a gap where a new piece of DNA can be added. Proteins: Complex molecules that play many critical roles in the body. They are DNA: A long molecule that carries a cell’s required for the structure, function and genetic information. regulation of the body’s tissues and organs.

Exon skipping: Exons are the sections of RNA: A molecule that is chemically similar DNA that code for proteins. In exon skip- to DNA and carries a matching code. Mes- ping, RNA is spliced together in a way that senger RNA (mRNA) helps cells translate causes cells to “skip over” an exon during the information found in genes into corre- protein production. sponding proteins.

Genes: Segments of DNA that act as Stop codon: A sequence within an mRNA blueprints for making proteins for virtually molecule that signals cells to halt protein every function and structure in the body. synthesis.

Gene-targeted therapy: The introduc- Vector: A delivery vehicle that carries new tion, removal or change in the content of genes to cells. Vectors may be genetically a person’s genetic code with the goal of disabled viruses, such as adenovirus, or treating or curing a disease. non-viral vectors, such as liposomes.

In contrast to AAVs, the American Society of Some strategies using anti- lentiviral vectors insert their Gene & Cell Therapy. “But sense oligonucleotides (ASOs) genetic cargo into the target there are limitations to the to alter the genetic machinery cell’s DNA. This means that AAV approach, such as size in different ways have made the new gene will be passed limit for the therapeutic it to late-stage human clinical on as cells divide, making gene and many patients’ trials or even through regu- lentiviruses useful when tar- pre-existing immunity latory approval in the United geting tissues that have high to AAV, so additional States and/or Europe. rates of cell turnover. approaches are needed.” One promising way of “The most promising using ASOs is through current approach for gene TARGETING antisense gene therapy that therapy to treat neuromus- GENE DEFECTS aims to “turn off ” a defective cular disease is the use of Working with technologies gene’s effect. This involves AAVs,” says Michele Calos, only dreamed of in the past, altering a strand of DNA or Ph.D., an MDA grantee and scientists are developing more RNA to effectively tell cells immediate past president of ways to target gene defects. to ignore part of the genetic >

Quest 20 ISSUE 2 • 2019

“ For many years MDA instructions during protein mutated gene. This approach manufacturing. This is called allows for a precise method of has invested in basic and exon skipping and can cause targeting genetic mutations, translational research that has cells to produce shortened but but because it permanently functional protein. changes the genome, it raises contributed to gene discovery Nonsense mutations are greater safety concerns. changes in DNA sequence Currently, gene editing is and therapeutic strategies that introduce a premature usually done ex vivo. Even- using gene therapy. In the era stop codon, which acts like tually, scientists hope to use a cellular stop sign, causing viral vectors to transport of clinical implementation of cells to stop partway through tools, such as CRISPR–Cas9, gene therapy, the MDA Care the protein-making process. into the body to edit genes, This results in shortened but more work is needed Center network will play an protein that does not work to determine if this is safe important role in establishing because it is missing critical in humans. parts. With stop codon read best practices for providing through technology, cells THERE ARE RISKS gene therapy treatments to can be coaxed into running Research and development of the erroneous stop sign, gene-targeted therapies are the patient community.” allowing them to produce being conducted with a sharp —Barry Byrne, M.D., Ph.D. functional protein. focus on patient safety, but Gene editing permits there are still risks associated scientists to go into a cell with efforts to alter a person’s and delete or replace a tar- genetic code. Some of the geted section of DNA in the risks are:

Quest 22 ISSUE 2 • 2019 • The body’s immune likely see more successful gene-targeted therapies, such system may mount a applications of new gene as Spinraza for SMA and response to the viral therapy technologies in the Exondys 51 for DMD. Many vector, which could lead to near future,” says MDA more experimental thera- inflammation and, possi- grantee Kleopas Kleopa, pies are in clinical trials for bly, organ failure. M.D., professor and senior diseases including limb-girdle • The immune system consulting neurologist at muscular dystrophy (LGMD) may mount a response to the Cyprus Institute of and Pompe disease. proteins previously not Neurology and Genetics, “As we learn more from expressed in a person that Cyprus School of Molecular the ongoing preclinical are now expressed with Medicine, in Nicosia, Cyprus. and clinical studies, the gene-targeted therapy. Over the last few decades, approaches for treating these • The therapy may not work MDA-supported research- disorders will continue to as predicted. In this case, ers have discovered the improve,” Dr. Kleopa says. there is no way to “turn gene-causing mutations for The outlook for gene- off ” a new gene once it is many neuromuscular disor- targeted therapies is hopeful, introduced to cells. ders, developed and refined as a robust pipeline of gene gene delivery tools and therapy candidates and new ERA OF HOPE methods, and devised creative technologies could soon ben- We are in an unprecedented and groundbreaking solutions efit individuals and families era of therapy development to the problems created by living with neuromuscular for neuromuscular diseases. genetic defects. diseases. Q “For the first time, we Those efforts have con- have seen the development tributed to the FDA approval Amy Madsen is a science of genetic therapies in the of Zolgensma, as well as writer and frequent contributor last few years, and we’ll approvals for other types of to Quest.

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SIGNS & TREATMENT SYMPTOMS TESTING OPTIONS SUPPORT RESOURCES

WHAT COULD SPINRAZA UNLOCK?

Lauren age 20 The ﬁ rst treatment for children and Later-onset (Type 3) SMA adults with spinal muscular atrophy (SMA) treated with SPINRAZA

Individual results may vary based on several factors, including severity of disease, initiation of treatment, and duration of therapy. SPINRAZA was evaluated in a well-controlled study of 126 individuals with later-onset (Types 2 and 3) SMA. The results are supported by an open-label study of 28 individuals with later-onset (Types 2 and 3) IMPORTANT FACTS ABOUT SPINRAZA® (nusinersen) SMA, aged 2 to 16 years at ﬁ rst dose. Limitations of the open-label study included differences in dosing USES compared with the approved regimen and the lack of an untreated group. SPINRAZA is a prescription medicine used to treat spinal muscular atrophy (SMA) in pediatric and adult patients.

WARNINGS Increased risk of bleeding complications has been observed after administration of similar medicines. Your Maintaining motor healthcare provider should perform blood tests before you start treatment with SPINRAZA and before each dose function over time Attend a SPINRAZA event to monitor for signs of these risks. Seek medical attention if unexpected bleeding occurs. Increased risk of kidney damage, including potentially fatal acute inﬂ ammation of the kidney, has been Individuals taking SPINRAZA Visit SPINRAZAevent.com or observed after administration of similar medicines. Your healthcare provider should perform urine testing before you start treatment with SPINRAZA and before each dose to monitor for signs of this risk. continued to improve or maintain call 1-888-615-4343 to motor function over nearly 3 years, connect with your local SMA COMMON SIDE EFFECTS regardless of their level of function community. • The most common side effects of SPINRAZA include lower respiratory infection, fever, constipation, headache, before starting treatment. vomiting, back pain, and post-lumbar puncture syndrome (headache related to the intrathecal procedure). • Serious side effects of complete or partial collapse of a lung or lobe of a lung have been reported. Talk to your healthcare provider about any side effect that bothers you or that does not go away. INDICATION SPINRAZA is a prescription medicine used to treat spinal muscular atrophy (SMA) in pediatric and adult patients. OTHER INFORMATION SPINRAZA is a medication that should be administered as an injection into the lower back (a procedure called IMPORTANT SAFETY INFORMATION intrathecal injection) by, or under the direction of, an experienced healthcare professional. Increased risk of bleeding complications has been observed after administration of similar medicines. Your Before taking SPINRAZA, tell your healthcare provider if you are pregnant or plan to become pregnant. healthcare provider should perform blood tests before you start treatment with SPINRAZA and before each dose to monitor for signs of these risks. Seek medical attention if unexpected bleeding occurs. QUESTIONS? The risk information provided here is not comprehensive. To learn more, talk about SPINRAZA with your Increased risk of kidney damage, including potentially fatal acute inﬂ ammation of the kidney, has been healthcare provider or pharmacist. The FDA-approved product labeling can be found at www.spinraza.com or observed after administration of similar medicines. Your healthcare provider should perform urine testing before 1-844-4SPINRAZA (1-844-477-4672). you start treatment with SPINRAZA and before each dose to monitor for signs of this risk. MANUFACTURED FOR The most common side effects of SPINRAZA include lower respiratory infection, fever, constipation, headache, Biogen vomiting, back pain, and post-lumbar puncture syndrome. Cambridge, MA 02142 revised 10/18 These are not all of the possible side effects of SPINRAZA. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Before taking SPINRAZA, tell your healthcare provider if you are pregnant or plan to become pregnant. For additional Important Safety Information, please see brief summary of full Prescribing Information on the next page. © 2018 Biogen. All rights reserved. 11/18 SPZ-US-1682V3 This information is not intended to replace discussions with your healthcare provider. 225 Binney Street, Cambridge, MA 02142

SPCO18CDNY5445_JournalAd_MDA_Updt_10_18_Label_r6.indd 1 11/14/18 3:34 PM ADVERTISEMENT ADVERTISEMENT

WHAT COULD SPINRAZA UNLOCK?

Lauren age 20 The ﬁ rst treatment for children and Later-onset (Type 3) SMA adults with spinal muscular atrophy (SMA) treated with SPINRAZA

SPCO18CDNY5445_JournalAd_MDA_Updt_10_18_Label_r6.indd 1 11/14/18 3:34 PM SPOTLIGHT SHEDDING LIGHT ON MYOTONIC DYSTROPHY Guiding Treatment for Myotonic Dystrophy A Q&A with neurologist Tetsuo Ashizawa, M.D.

Can you explain the genetic component of DM? DM1 results from a mutation in the DMPK gene and DM2 from a mutation in the CNBP gene. The mutation in the DMPK gene leads to an expansion of a cytosine-thymine-guanine (CTG) trinucleotide repeat in the DNA. (Nucleotides are molecules that make up DNA and RNA.) Normally, we have up to 37 CTG repeats at this location. But most of those with DM have a much higher number of repeats, sometimes in the thousands. In DM1, the yotonic adolescence or adulthood, in adulthood and tends to be larger the repeat, the earlier dystrophy typically with myotonia. less severe than DM1. the symptoms appear and the M(DM) is the most Over time, the muscles Numerous medical condi- more severe they are. Also, the common form of muscular throughout the body tions occur with both forms, number of repeats in DM1 may dystrophy in adults. This is a become weaker and other including cardiovascular com- increase with each generation. complex disease, affecting not organs are affected. plications, gastrointestinal So while a grandparent may just the muscles but nearly • Juvenile onset begins symptoms (in DM1), a higher have few symptoms, a grand- every other organ system between ages 1 and 10. risk of certain cancers, male child may have many. This is in the body. The signature It is characterized by infertility and low testoster- called “genetic anticipation.” manifestation is myotonia, an cognitive and behavioral one, high cholesterol and low The mutated gene, in turn, inability to consciously relax symptoms, including atten- blood pressure, and insulin produces an expanded version the muscles, coupled with tion deficit disorder and resistance. of messenger RNA, which is progressive muscle weakness. anxiety, as well as muscle We turned to Tetsuo responsible for reading the There are two types of weakness and myotonia. Ashizawa, M.D., a professor DNA “code.” These RNA DM, each caused by a differ- • Congenital onset begins at of neurology and director of molecules become toxic and ent genetic mutation. or before birth and features the Neurosciences Research interfere with the production DM1 is the most common severe muscle weakness, Program at Houston Method- of other proteins, preventing form, with three subtypes: cognitive impairment and ist and Weill Cornell Medical normal cell functioning. • Adult onset, also called other developmental College, and a leading expert “classical DM,” is the most abnormalities. in DM, for an update on treat- Is there any treatment common type, affecting DM2, sometimes called ment and efforts to find a cure for DM? about 75 percent of those proximal myotonic myopathy for the disease. Most of what We can treat the symptoms. with DM. It begins in (PROMM), typically begins you’ll read here refers to DM1. There are some medications

Quest 26 ISSUE 2 • 2019 difficulty finding and access- and age-related differences ing quality care and informed in the disease. There are Find a Trial clinicians. The newly pub- two registries: Myotonic Learn what to expect in lished recommendations are Dystrophy Family Registry, a clinical trial and find intended to help standardize managed by the Myotonic out if there is a study you and elevate care for people Dystrophy Foundation, and can enroll in at mda.org/ living with DM. the Myotonic Dystrophy and research/clinical-trials. Facioscapulohumeral Muscu- Where is the research on lar Dystrophy Registry, run finding a cure for DM? by the National Institute of A better understanding of the Neurological Diseases and Tetsuo Ashizawa, M.D disease is driving research Stroke. People with DM can into new targets for treat- enroll in both. that can help improve myo- ment, most directed at the They can also volunteer tonia and muscle pain (which toxic RNA. These include for clinical studies. There are primarily occurs in DM2). antisense oligonucleotides numerous ongoing clinical People with DM may (ASOs). The ASO binds to trials investigating everything develop problems with the target RNA and destroys from drugs that target the arrhythmias, or irregular it, thus restoring function. disease itself to treatments for heartbeats, which can lead While successful in animal the complications and genetic to heart failure and sudden models, the one human clini- studies to better understand death. Thus, people with cal trial so far didn’t show any how the disease manifests in DM often receive a pacemaker clinically detectable therapeu- families. Q or defibrillator. tic effects. Now researchers Exercise is a good idea. are working on a better We used to think that DM delivery system for humans. Total toileting solution that muscles are fragile and break If ASOs can be delivered to hygienically cleans you then lifts down easily, but it turns out muscles and other organs, you to standing. that regular physical activity it may address many of the may prevent muscle atrophy. complications of the disease. However, it is important that Another option is to use a people with DM check with genetic tool called CRISPR their doctor before beginning to remove the expanded DNA any exercise program. repeat from the gene itself. But that is 10 to 20 years Are there guidelines down the road. for diagnosing and treating DM? What can those with The first-ever Consensus- DM do today to help Based Care Recommendations advance research? for Adults with Myotonic They can enroll in a registry Dystrophy Type 1 were that helps recruit people for published last year. Currently, clinical studies. They also there are no evidence-based can participate in longitudi- guidelines to establish a stan- nal natural history studies. • Adjustable Seat Tilt dard of care for patients with Understanding the natural • Installs Easily DM because the rigorous history of the disease is • Electric Washing Bidet clinical studies needed to important for future clini- • $100 Off Accessories gather the necessary data cal trials in order to track have yet to be conducted. the efficacy of drugs and Thus, many patients report understand ethnic, gender (877) 665-4381 liftseat.com SPONSORED ADVERTISING CONTENT MAKING THE MOST OF EVERY MOMENT The role of a caregiver By Grace Grutter The moment you become a parent of a child with spinal muscular atrophy (SMA), everything changes. My daughter, Nella, was diagnosed with SMA when she was 11 weeks old, and the doctors warned me and my husband that she would only get weaker over time since her condition was terminal. We cherished every moment that we had with Nella, and it was important to us to spend time seeking out possible treatment and care, even though we were told treatment for SMA was not available at the time of her diagnosis. For months, Nella struggled to swallow or move unaided. She had to sleep with a ventilator to help her breathe throughout the night. For such a young life, it seemed unfair that she had so many challenges to face. Individual results may vary based on several factors, including severity of disease, initiation of treatment, In 2016, we first heard about a clinical trial for SPINRAZA® (nusinersen), and duration of therapy. a potential treatment for SMA. The trial was taking place in Orlando, Florida, and would have required our family to move across the country, so we did not have Nella participate. Instead, I decided to immerse myself in the SMA community and follow the journeys receiving treatment, and reaching milestones we never of those accessing treatment. It was through this community that I thought possible. In June 2018, Nella completed her eighth learned the trial would be expanding its access to a hospital near SPINRAZA injection and shortly afterwards, she our home in St. Louis, Missouri. We consulted with our doctor to celebrated her fifth birthday. She continues to surprise us – discuss the risks and benefits, and in December 2016, Nella received recently during physical therapy she turned her head almost her first loading dose of SPINRAZA as part of the trial. Weeks later, 180 degrees all on her own. Some may consider this to be SPINRAZA was approved by the FDA for treatment in adults and a small movement, but it isn’t small for us – it’s everything! children. I get chills thinking about the enormous feelings of hope Every caregiver has their own unique experience, but and gratitude I felt as Nella received her first injection of SPINRAZA. despite these different experiences I know there is one thing At her diagnosis, doctors had told us that there was no treatment we all have in common – it’s that we make the most of every and to prepare for our daughter to pass. And yet, here she is – alive, moment with our loved ones.

INDICATION These are not all of the possible side effects of SPINRAZA. SPINRAZA® (nusinersen) is a prescription medicine used to treat Call your healthcare provider for medical advice about side spinal muscular atrophy (SMA) in pediatric and adult patients. effects. You may report side effects to FDA at IMPORTANT SAFETY INFORMATION 1-800-FDA-1088. Increased risk of bleeding complications has been observed after Before taking SPINRAZA, tell your healthcare provider administration of similar medicines. Your healthcare provider should if you are pregnant or plan to become pregnant. perform blood tests before you start treatment with SPINRAZA and For additional Important Safety Information, please before each dose to monitor for signs of these risks. Seek medical see brief summary of full Prescribing Information on attention if unexpected bleeding occurs. the next page. Increased risk of kidney damage, including potentially fatal acute This information is not intended to replace discussions has been observed after administration inflammation of the kidney, with your healthcare provider. of similar medicines. Your healthcare provider should perform urine testing before you start treatment with SPINRAZA and before each dose to monitor for signs of this risk. The most common side effects of SPINRAZA include lower respiratory infection, fever, constipation, headache, vomiting, back pain, and post-lumbar puncture syndrome.

Biogen is compensating Grace for sharing her and Nella’s story. This content has been reviewed for compliance with FDA guidelines. Please keep in mind these are Nella’s experiences with SMA Type 1 and SPINRAZA, and others may have different experiences. For more information about SPINRAZA, visit SPINRAZA.com.

SPZ-US-2143v2 04/19

BGN8004_Spinraza_Advertorial_Grace_M03_print.indd 1 4/26/19 3:14 PM IMPORTANT FACTS ABOUT SPINRAZA® (nusinersen)

USES SPINRAZA is a prescription medicine used to treat spinal muscular atrophy (SMA) in pediatric and adult patients.

WARNINGS Increased risk of bleeding complications has been observed after administration of similar medicines. Your healthcare provider should perform blood tests before you start treatment with SPINRAZA and before each dose to monitor for signs of these risks. Seek medical attention if unexpected bleeding occurs. Increased risk of kidney damage, including potentially fatal acute inflammation of the kidney, has been observed after administration of similar medicines. Your healthcare provider should perform urine testing before you start treatment with SPINRAZA and before each dose to monitor for signs of this risk.

COMMON SIDE EFFECTS • The most common side effects of SPINRAZA include lower respiratory infection, fever, constipation, headache, vomiting, back pain, and post-lumbar puncture syndrome (headache related to the intrathecal procedure). • Serious side effects of complete or partial collapse of a lung or lobe of a lung have been reported. Talk to your healthcare provider about any side effect that bothers you or that does not go away.

OTHER INFORMATION SPINRAZA is a medication that should be administered as an injection into the lower back (a procedure called intrathecal injection) by, or under the direction of, an experienced healthcare professional. Before taking SPINRAZA, tell your healthcare provider if you are pregnant or plan to become pregnant.

QUESTIONS? The risk information provided here is not comprehensive. To learn more, talk about SPINRAZA with your healthcare provider or pharmacist. The FDA-approved product labeling can be found at www.spinraza.com or 1-844-4SPINRAZA (1-844-477-4672).

MANUFACTURED FOR Biogen Cambridge, MA 02142 revised 11/18

SPZ-US-2143v2 04/19

BGN8004_Spinraza_Advertorial_Grace_M03_print.indd 2 4/26/19 3:14 PM Your guide to the MDA community, from news briefs to access MDA inspiring profiles Above and Beyond One doctor gives his all at MDA Summer Camp

From the moment neurologist my patients on a daily basis. Heeren Patel, M.D., was asked I understand them better.” to be a volunteer on-call phy- By donating his time, Dr. sician at MDA Summer Camp Patel has helped keep down in northern Illinois, he already camp medical costs, and he has wanted to do more to help. helped with recruitment and Rather than just being called in retention of volunteer medical the event of an emergency, he staff. Within his local medical had another idea. community, he has worked to

“I asked, ‘What if I came make it easier for doctors and Dr. Patel says working with kids at MDA Summer Camp is “life-changing.” and provided care on-site?” nurses to take time off for vol- Dr. Patel says. unteer opportunities like these. award because it has motivated for them to have the experience. That’s exactly what he did. For all of his efforts, he was his peers to help. “Once you do it, you For the past five summers, he awarded a Humanitarian Award “So many nurses and realize the impact it makes has eagerly spent one week by Northwestern Medicine in doctors have said they want to on you, all while providing a of his vacation time at MDA January. Given in honor of Mar- get involved,” he says. “Now we safe, impactful environment Summer Camp. tin Luther King Jr., the award have a nice cohort of medical for the campers to have fun “It is such a life-changing recognizes Dr. Patel’s contri- staff we can lean on if we need and build their confidence,” experience,” says Dr. Patel, who butions to the MDA Summer it at the camp.” he says. “It almost feels selfish works for Northwestern Med- Camp program. For this summer, Dr. Patel because of how good it feels icine in the Chicago area. “It’s True to his humble nature, already has four new volunteer to help. It’s humbling and changed the way I practice with Dr. Patel is most proud of this nurses, and he says he is excited a privilege.”

Marathon Momentum MARCH WAS Nura Maali (fourth from FOR MDA left), a mother of two kids SHAMROCKS with limb-girdle muscular What: The nation’s dystrophy (LGMD), gathered largest St. Patrick’s Day a team of eight and joined fundraiser MDA Team Momentum for Started: 1982 the TCS New York City Marathon last November. This year: $7.3 million+ raised Her team raised nearly $30,000, and she’s excited Since 1982: $330 million+ to fundraise again for the raised Bank of America Chicago How: Retail campaigns, Marathon in October. special events, Green “Running in honor of Day for MDA and online fundraising my kids, raising awareness and seeing their faces as I Fun fact: More than crossed the finish line meant 20,000 retail partners sold Shamrocks this year. more to me than anything,” Maali says.

Quest 30 ISSUE 2 • 2019 ADVERTISEMENT FROM WHERE I SIT UNFILTERED VOICES FROM THE MDA COMMUNITY Pushing Limits A hiker proves she is stronger than FSHD by taking on the toughest trek of her life

BY NEENAH WILLIAMS

it turned out to be a major the time I made it to the top. Neenah Williams at the benefit during my trek. At one point mid-climb, summit of Mount Kilimanjaro in Tanzania On top of that, I took my I was overcome with emotion. first hot yoga class, which Tears flowed as I sat on a quickly turned into a habit rock, overwhelmed by grate- that helped improve my lung fulness, pride and the reality efficiency. My yoga teacher of how FSHD has changed was an expert on the effects my body over the years. of high altitude on the body, On Oct. 8, 2018, I made and he provided me with diet it to the summit of Mount tips to help give my muscles Kilimanjaro, known as Uhuru more endurance. Peak. I have never felt as Approximately three weeks strong or as equal as I did before my climb, I found a on that day. group of local hiking buddies, I say “equal” because the and together we summited night I began my trek from base Pikes Peak (14,115 feet). camp, I was climbing along- fter six long days, I’m Just after Christmas in This gave me an idea of how side several hundred complete tired. It’s the middle 2017, I decided I wanted to do my body would react as I strangers, all contending with Aof the night, I’m something spontaneous and ascended Kilimanjaro. their own internal struggles. wearing five layers of clothing unforgettable in 2018. A cou- It is as if all of these things No one knows anything about and I know I have several ple of weeks later (somewhat fell into place at the perfect your story, yet there’s this one more hours to go in the on a whim), I booked a trip time, one right after the other. goal that aligns everyone there. frigid air before I reach the to climb Mount Kilimanjaro, Isn’t it beautiful how things I wasn’t known as Neenah, the 19,341-foot summit. “Mom Africa’s tallest mountain. work out? girl with FSHD. Instead, I was believes in you. Dad believes In the months following simply one in a group of people in you. All of your friends and my decision, FSHD unex- ON TOP OF who all saw in each other the family believe in you. You are pectedly began to affect my THE WORLD same resilient spirit and desire strong,” are the words that lower limbs. When hiking, Each day of the Kilimanjaro to keep pressing forward, no echo through my mind with I began to fall on the trails. journey came with its own matter how much our bodies every step. When I planned the trip, challenges. Not only was the begged us to quit. I am not one who believes I had no idea the timeline climate different from one day To all my friends, this in chance. Everything hap- was going to correspond so to the next — the trek begins condition does not define us. pens for a reason. For the closely with this gradual in a rainforest and ends in a It is only one of many factors past decade, facioscapulohu- decline in muscle. I quickly frozen desert — but the alti- that shape our mind, body and meral muscular dystrophy learned that the trek was tude gain and steep inclines spirit. The strength within is (FSHD) has been part of my going to be challenging. make it tough to breathe a powerful force. Keep push- story. It has never been who while carrying a full day pack. ing your limits, and soon you I am. In fact, it has only FALLING INTO PLACE On day four, we spent will be on top of the world. Q served to enhance the whole In August 2018, I moved to several hours climbing up the person that I am, gradually Colorado. The elevation of my side of a daunting cliff known Neenah Williams, 27, was putting up hurdles that I city is more than a mile high. as Barranco Wall. The wall is diagnosed with FSHD in 2007. work to jump over and Living at this altitude took more than 800 feet tall, and She lives in Colorado and is an grow from. a lot of getting used to, but my hips were throbbing by avid hiker and yogi.

Quest 32 ISSUE 2 • 2019 With a ton of ways to increase your independence at Abilities Expo, your glass really is half full!

• Cutting-edge products and services • Get answers from the experts • Adaptive sports for better health • Informative workshops • Service animals open doors • Inclusive dance empowers • Daily living aids FREE • Therapeutic cannabis: Real facts ADMISSION • Life-changing activities for all ages

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Quest.indd 1 4/25/19 7:26 AM LASTING IMPRESSION A Family Affair Brotherly love fuels fire fighter’s dedication to Fill the Boot

Clockwise from above: MDA supporter Neil Kramer with San Marcos fire fighters; Captain Mike Vasile; Vasile and his brother Cole, who has DMD. Give Us Your Best Shot! or Captain Mike Vasile, a member of San Marcos, Calif., Local 4184, Fill the Boot Enter the Lasting is personal. Impression Photo Contest F Vasile’s younger brother, Cole, was diagnosed with Duchenne muscular dystrophy by Aug. 30, 2019 (DMD) at age 5. Although doctors expected him to live only into his mid-20s, Cole is now 32. We want to recognize you, our “Unfortunately, I have seen quite a few people succumb to the disease — good people who were readers, and the extraordinary taken way too early,” Vasile says. “I always enjoy raising awareness and funds for MDA to help moments in your lives. Share support those with the disease and to hopefully someday find a cure.” a photo of a meaningful Each year, Vasile organizes his local Fill the Boot Drive. He and about 35 of his fellow off-duty moment for you or a loved fire fighters gather at an intersection for eight hours to collect donations for MDA. Cole always one with a neuromuscular comes out to motivate the fire fighters, and an enthusiastic community rallies behind the event. disease, and it could be In 2018, they raised $22,514. selected to appear right “Our event wouldn’t be successful without the participation and support of our local members here, in Lasting Impression, and those who are passing through making the donations,” Vasile says. in a future issue of Quest. Vasile is already busy planning the 2019 San Marcos Fill the Boot, which will take place on All photo entries must be Friday, Oct. 4. submitted by Aug. 30, 2019 “We are looking forward to another successful year and helping to achieve a common goal, at surveymonkey.com/r/ which is to make a difference,” Vasile says. questphoto.

Quest 34 ISSUE 2 • 2019